Although Drosophila melanogaster is a model system for the molecular genetics of innate immunity, virtually nothing is known about the life history and virulence strategies of its natural parasites. Parasitic wasps can infect Drosophila larvae at frequencies greater than 50% in natural populations, and are highly amenable to laboratory and field study. The Schlenke lab has developed a collection of 17 live wasp parasite strains of Drosophila, and robust protocols for extracting and manipulating the venom cocktails they use to thwart the host cellular encapsulation response mounted against their eggs. In this application, Schlenke proposes to use a joint transcriptomic and proteomic approach to identify the venom gland contents of 10 related wasp species that are highly successful infectors of D. melanogaster. He will then assay the effects of whole venom from each wasp species using two types of assays: First, he will assay the effects of venom on the structure and function of D. melanogaster hemocytes ex vivo. Second, he will assay encapsulation defects in vivo by injecting oil droplets into flies, which are readily melanotically encapsulated, mixed with venom fractions. For any immune suppressive effects that whole venom has, Schlenke will then identify venom fractions and individual venom proteins responsible for these characterized venom effects. Finally, Schlenke will use population genetic and molecular evolution approaches to uncover how venoms maintain virulence function in their co-evolutionary arms race with host immune systems. In sum, Schlenke hopes to develop the Drosophila-wasp system as a model for the study of eukaryotic host-pathogen interactions and for the evolution of parasite life histories.